mortality/aging

• premature death
  • mice show increased survival relative to SNCA-null transgenic animals, but survival is reduced relative to wild-type or SNCA-null mice
  (MGI Ref ID J:124976)

nervous system phenotype

• abnormal channel response
  • approximate 40% reduction of maximal A-type Kv4.3 potassium conductances in dopaminergic substantia nigra neurons of middle-aged mice
  (MGI Ref ID J:216589)
  • intracellular dialysis of the reducing agent glutathione rescues the A-type K channel dysfunction
  (MGI Ref ID J:216589)

• abnormal nervous system electrophysiology
  • dopaminergic substantia nigra neurons from young (3-4 months) adults already show faster in vivo firing frequencies compared to controls, with mean firing frequencies about 50% higher, however, differences in action potential repolarization are not yet apparent at 3-4 months of age
  (MGI Ref ID J:216589)
  • Normal - however, electrical activity of dopaminergic ventral tegmental area neurons is not altered
  (MGI Ref ID J:216589)
  • middle-aged (7-8 months) dopaminergic substantia nigra neurons show an approximate 100% increase in mean firing rates, prolonged action potential repolarization, and more prominent pacemaking patterns
  (MGI Ref ID J:216589)
  • parent at 3-4 months of age
  (MGI Ref ID J:216589)
  • the regularity of firing is lower in 3 month old dopaminergic substantia nigra neurons
  (MGI Ref ID J:216589)

• abnormal neuron physiology
  • middle-aged (7-8 months) dopaminergic substantia nigra neurons show an approximate 100% increase in mean firing rates, prolonged action potential repolarization, and more prominent pacemaking patterns, with faster firing frequencies seen already at 3-4 months of age
  (MGI Ref ID J:216589)
  • nths of age
  (MGI Ref ID J:216589)

behavior/neurological phenotype

• decreased grip strength
  • grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)
  (MGI Ref ID J:86222)

• decreased vertical activity
  • progressive reduction in rearing behavior is observed in animals at 6, 18, and 24 months of age, with notably decreased activity apparent at 3 months of age
  (MGI Ref ID J:86222)

• impaired coordination
  • up to 4 months of age, mutants perform better than controls on the accelerating rotating rod, but beyond 4 months, display progressive difficulties maintaining balance
  (MGI Ref ID J:86222)

• short stride length
  • step length of transgenic animals is reduced relative to wild-type (1.9 cm vs 2.25 cm in wild-type)
  (MGI Ref ID J:86222)

• weakness
  • grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)
  (MGI Ref ID J:86222)

nervous system phenotype

• abnormal neurite morphology
  • signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed
  (MGI Ref ID J:86222)

• absent long term depression
  • corticostriatal long-term depression (LTD) is absent in old, but not young, mutants
  (MGI Ref ID J:181820)
  • dopamine does not restore LTD in old mice, however, zaprinast, an inhibitor of phosphodiesterases, restores LTD
  (MGI Ref ID J:181820)
  • Normal - mice, however, do not exhibit age-related differences in striatal excitability
  (MGI Ref ID J:181820)

• alpha-synuclein inclusion body
  • accumulation of human alpha-synuclein is seen in nerve terminals and cell bodies in the dorsal motor nucleus of the vagus nerve and in axon terminals innervating the gastric myenteric plexus, although accumulation is diffuse and does not show Lewy body-like appearance
  (MGI Ref ID J:185489)
  • ke appearance
  (MGI Ref ID J:185489)

• neurodegeneration
  • at 7 months of age, such abnormalities are seen only occasionally in the neocortex and hippocampus, but are frequently seen in a dense network of neurites in the olfactory bulb
  (MGI Ref ID J:86222)
  • signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed
  (MGI Ref ID J:86222)

digestive/alimentary phenotype

• abnormal defecation
  • stool frequency is normal at 2 months of age but is 15%, 21%, and 40% lower at 9, 15, and 19 months of age, respectively
  (MGI Ref ID J:185489)
  • total wet weight of stool and stool water content are lower in 19 month old mice compared to controls, however stool dry weight is no different and food intake and body weight are similar to controls
  (MGI Ref ID J:185489)

• abnormal digestion
  • mice show a decline in gastric emptying with age, with twice as much residual food remaining in the stomachs of 20 month old mutants as in controls
  (MGI Ref ID J:185489)

mortality/aging

• premature death
  • increased mortality rate in the first 180 days as compared to wild-type controls
  (MGI Ref ID J:214065)